David M. Jacobs

Use of ceftaroline after glycopeptide failure to eradicate meticillin-resistant Staphylococcus aureus bacteraemia with elevated vancomycin minimum inhibitory concentrations

Elevated minimum inhibitory concentrations (MICs) of vancomycin against meticillin-resistant Staphylococcus aureus (MRSA) and the emergence of heteroresistant S. aureus strains have led to increased use of anti-MRSA antibiotics other than vancomycin. Ceftaroline fosamil is a novel cephalosporin with activity against MRSA, but there are limited clinical data on its use for MRSA bacteraemia (MRSAB) and against strains exhibiting high vancomycin MICs (2-4 μg/mL). This multicentre, retrospective, case-control study compared the microbiological and clinical effectiveness of ceftaroline used after vancomycin failure with that of vancomycin-treated controls for the treatment of MRSA with vancomycin MICs ≥ 2 μg/mL. In total, 32 patients were matched 1:1 with respect to vancomycin MIC, age and origin of bacteraemia. In the ceftaroline group, patients received prior MRSA therapy for a median of 5 days [interquartile range (IQR), 3-15.8 days] prior to switching to ceftaroline. Median time to eradication of MRSA was significantly less after treatment with ceftaroline compared with vancomycin [4 days (IQR, 3-7.5 days) vs. 8 days (IQR, 5.8-19.5 days); P=0.02]. Both clinical success at the end of treatment and recurrence of MRSA at Day 7 were trending towards being inferior in the vancomycin group, although the results did not attain statistical significance [81% vs. 44% (P=0.06) and 6% vs. 38% (P=0.08), respectively]. Ceftaroline added at the point of vancomycin failure resolves MRSAB more rapidly and with a higher rate of clinical success, therefore ceftaroline should be considered as an alternative for these difficult-to-treat infections.

Distal small bowel bypass for weight regain after gastric bypass: safety and efficacy threshold occurs at<70% bypass

BACKGROUND For patients with poor weight loss (WL) after Roux-en-Y gastric bypass (RYGB) there are few well-tolerated and effective surgical options. Revision to distal bypass by shortening of the common channel (CC) induces significant WL but often produces protein calorie malnutrition (PCM) and severe diarrhea. OBJECTIVE The aim of this study was to identify a safe and effective threshold for distal small bowel bypass when done for revision of gastric bypass. SETTING Academic Institution, United States. METHODS We performed revision of RYGB for WL in 20 patients by shortening the CC to a new length of 120-300 cm. The Roux limb length was unchanged. WL and PCM were monitored. A threshold for percent of small bowel bypassed at which PCM was avoided was retrospectively determined. WL was then compared in patients above and below this threshold. Five patients completed a 250-kcal mixed meal challenge before and 3 months after revision to determine selected gut hormone responses. RESULTS Bypassing ≥70% small bowel resulted in PCM in 4 of 10 patients but in none of 10 patients below that threshold. PCM was observed as late as 2 years after revision and necessitated rerevision by lengthening of the CC in 3 patients. Additionally, nocturnal diarrhea was more common and more intractable when ≥70% bypass was done. Both groups had significant excess body WL over 2 years, but it was greater in patients with ≥70% bypass (47±19 versus 26±17; P<.05). A favorable gut hormone response was observed with 3-hour decrease in glucose-dependent insulinotropic peptide (GIP) by 25% and increase in glucagon-like peptide-1 (GLP-1) by 25%, whereas fasting peptide-YY (PYY) increased by 71% (P<.05 for all). CONCLUSIONS Revision of RYGB to distal bypass when it is <70% of a patients small bowel length results in an acceptable balance of WL and a positive safety profile. WL may be mediated through an enhanced gut hormone effect, an aversion to ingested fat, and possibly other mechanisms.

Evaluating the impact of a pharmacist’s absence from an antimicrobial stewardship team

PURPOSE Results of a study to determine the impact of a clinical pharmacists temporary absence from a hospitals antimicrobial stewardship team are presented. METHODS A retrospective chart review was conducted to compare the appropriateness of the use of selected antimicrobial medications with and without regular pharmacist involvement on the hospitals antimicrobial stewardship team. The charts of two samples of patients were evaluated: (1) 119 patients who had received prolonged (≥72 hours) imipenem-cilastatin, linezolid, or micafungin therapy over a three-month period during which a clinical pharmacist routinely provided interventions to help ensure the drugs were used according to institutional guidelines and (2) 111 patients treated with one of the three drugs during a three-month period when the clinical pharmacist did not serve on the stewardship team. RESULTS Relative to the period of active pharmacist involvement in antimicrobial stewardship, rates of inappropriate use of imipenem-cilastatin, linezolid, and micafungin during the pharmacists absence were deemed to have increased by 27, 39, and 35 percentage points, respectively, with corresponding increases in the average duration of therapy of 0.7, 4.0, and 3.2 days; in addition, the number of cases of Clostridium difficile infection increased more than threefold (from 8 to 25) during the pharmacists absence. CONCLUSION The temporary absence of a pharmacist from the antimicrobial stewardship team was associated with increased rates of inappropriate use of restricted antimicrobial agents and consequent increases in average durations of therapy.

Post-surgical mediastinitis due to carbapenem-resistant Enterobacteriaceae: Clinical, epidemiological and survival characteristics

Invasive infections due to carbapenem-resistant Enterobacteriaceae (CRE), including polymyxin-resistant (PR-CRE) strains, are being increasingly reported. However, there is a lack of clinical data for several life-threatening infections. Here we describe a cohort of patients with post-surgical mediastinitis due to CRE, including PR-CRE. This study was a retrospective cohort design at a single cardiology centre. Patients with mediastinitis due to CRE were identified and were investigated for clinically relevant variables. Infecting isolates were studied using molecular techniques. Patients infected with polymyxin-susceptible CRE (PS-CRE) strains were compared with those infected with PR-CRE strains. In total, 33 patients with CRE mediastinitis were studied, including 15 patients (45%) with PR-CRE. The majority (61%) were previously colonised. All infecting isolates carried blaKPC genes. Baseline characteristics of patients with PR-CRE mediastinitis were comparable with those with PS-CRE mediastinitis. Of the patients studied, 70% received at least one agent considered active in vitro and most patients received at least three concomitant antibiotics. Carbapenem plus polymyxin B was the most common antibiotic combination (73%). Over 90% of patients underwent surgical debridement. Overall, in-hospital mortality was 33% and tended to be higher in patients infected with PR-CRE (17% vs. 53%; P=0.06). In conclusion, mediastinitis due to CRE, including PR-CRE, can become a significant challenge in centres with CRE and a high cardiac surgery volume. Despite complex antibiotic treatments and aggressive surgical procedures, these patients have a high mortality, particularly those infected with PR-CRE.

A call to action for outpatient antibiotic stewardship

OBJECTIVES To address the public health threat of antibiotic resistance, there has been an enhanced call for antibiotic stewardship programs throughout the health care continuum. SUMMARY While antibiotic stewardship programs have been well described in the inpatient setting, data on effectiveness and guidance on implementing outpatient programs is scarce. Establishing stewardship practices in the outpatient setting is necessary because more than 60% of human antibiotic use occurs in this setting. CONCLUSION In this article, we highlight the importance and need for stewardship in the outpatient setting, discuss strategies for the development of stewardship teams, and discuss potential metrics that can be used to assess effectiveness of antibiotic stewardship interventions.

Outpatient antibiotic stewardship: Interventions and opportunities

Improving the use of antibiotics across the continuum of care is a national priority. Data outlining the misuse of antibiotics in the outpatient setting justify the expansion of antibiotic stewardship programs (ASPs) into this health care setting; however, best practices for outpatient antibiotic stewardship (AS) are not yet defined. In a companion article, we focused on recommendations to overcome challenges related to the implementation of an outpatient ASP (e.g., building the AS team and defining program metrics). In this document, we outline AS interventions that have demonstrated success and highlight opportunities to enhance AS in the outpatient arena. This article summarizes examples of point-of-care testing, policies and interventions, and education strategies to improve antibiotic use that can be used in the outpatient setting.

Educational Testing Validity and Reliability in Pharmacy and Medical Education Literature

Objectives. To evaluate and compare the reliability and validity of educational testing reported in pharmacy education journals to medical education literature. Methods. Descriptions of validity evidence sources (content, construct, criterion, and reliability) were extracted from articles that reported educational testing of learners’ knowledge, skills, and/or abilities. Using educational testing, the findings of 108 pharmacy education articles were compared to the findings of 198 medical education articles. Results. For pharmacy educational testing, 14 articles (13%) reported more than 1 validity evidence source while 83 articles (77%) reported 1 validity evidence source and 11 articles (10%) did not have evidence. Among validity evidence sources, content validity was reported most frequently. Compared with pharmacy education literature, more medical education articles reported both validity and reliability (59%; p<0.001). Conclusion. While there were more scholarship of teaching and learning (SoTL) articles in pharmacy education compared to medical education, validity, and reliability reporting were limited in the pharmacy education literature.

Prevalence of and outcomes from Staphylococcus aureus pneumonia among hospitalized patients in the United States, 2009-2012

HighlightsThis longitudinal study used the National Inpatient Sample database, the largest publicly available all‐payer hospital discharge database in the United States, which is representative of the adult U.S. population.The prevalence of methicillin‐resistant Staphylococcus aureus pneumonia is declining in the hospitalized population in the United States.The decrease in methicillin‐resistant Staphylococcus aureus is accompanied by improvements in mortality and length of hospital stay.Vigilance for methicillin‐resistant Staphylococcus aureus must continue, with antimicrobial stewardship providing an opportunity for early vancomycin withdrawal or empirical withholding. Background: The burden of Staphylococcus aureus pneumonia is unknown despite being a major cause of mortality. We investigated national estimates of methicillin‐resistant S aureus (MRSA) and methicillin‐susceptible S aureus (MSSA) pneumonias and predictors of in‐hospital mortality and hospital length of stay (LOS). Methods: This was a retrospective analysis of the National Inpatient Sample from 2009‐2012. Adult patients with an ICD‐9‐CM primary diagnosis code for MRSA or MSSA pneumonia were included. Data weights were used to derive national estimates. Prevalence rates were reported per 100,000 hospital discharges, with trends presented descriptively. Results: There were 104,562 patients who had a primary diagnosis of S aureus pneumonia, with 81,275 from MRSA. MRSA pneumonia prevalence decreased steadily from 2009 (75.6 cases per 100,000 discharges) to 2012 (56.6 cases per 100,000 discharges), with MSSA pneumonia experiencing a slight decrease. Mortality rates decreased between 2009 and 2012 for MRSA pneumonia (7.9% to 6.4%) and MSSA pneumonia (6.9% to 4.7%; P = .008). LOS was higher for MRSA (6.9‐7.8 days) compared with MSSA (6.1‐6.4 days). Conclusions: The prevalence of MRSA pneumonia has decreased among hospitalized adults in the United States in recent years accompanied by improvements in mortality and LOS. Although the prevalence of MRSA pneumonia is declining, national vigilance is still warranted.

Trends in pneumococcal meningitis hospitalizations following the introduction of the 13-valent pneumococcal conjugate vaccine in the United States

BACKGROUND The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2010 in the U.S. and its impact on pneumococcal meningitis (PM) is unknown. We assessed the impact of PCV13 on PM hospitalization rates 4years after the vaccine was introduced. METHODS This was a retrospective analysis of the National Inpatient Sample from 2008-2014. Patients with an ICD-9-CM code for PM (320.1) were identified and rates calculated using US Census data as the denominator. Data weights were used to derive national estimates. We examined three time periods: 2008-2009 (late post-PCV7), 2010 (transition year), and 2011-2014 (post-PCV13). RESULTS During the study period, there were 10,493 hospitalizations due to PM in the U.S. Overall, PM incidence decreased from 0.62 to 0.38 cases per 100,000 over this time (39% decrease; P<0.01). Among children <2years, the average annualized PM rate decreased by 45% from 2.19 to 1.20 per 100,000 (P=0.10). Annual PM rates decreased in those aged 18-39years (0.25-0.15 cases per 100,000; P=0.02) and 40-64years (0.95-0.54 cases per 100,000; P=0.03). A total of 1016 deaths were due to PM, and the case fatality rate was variable over the study period (8.3%-11.2%; P=0.96). CONCLUSION Following the introduction of PCV13, hospitalization rates for PM decreased significantly with no subsequent improvements in case-fatality rate.

Early Administration of Adjuvant β-Lactam Therapy in Combination with Vancomycin among Patients with Methicillin-Resistant Staphylococcus aureus Bloodstream Infection: A Retrospective, Multicenter Analysis

To determine whether early administration of adjuvant β‐lactam in combination with vancomycin (COMBO) affects clinical outcomes compared to standard vancomycin therapy alone (STAN) among patients with methicillin‐resistant Staphylococcus aureus (MRSA) bloodstream infection.